Since its inception ten years ago, the GRASP Digestive Disease Center has promoted basic research at New England Medical Center and Tufts University Schools of Medicine and Veterinary Medicine. Current membership includes approximately 40 MD and PhD investigators who interact scientifically within the context of the Centers four Cores. Cores include 1) INTESTINAL MICROBIOLOGY, a service core with unique facilities capable of providing large and small cultures of bacterial and parasitic pathogens, and purified, biologically active toxins and other macromolecules. Cell Culture assists investigators in immortalizing and establishing novel epithelial cell lines from gastrointestinal tissues as well as maintaining specific cell lines for Center scientists; 2) MOLECULAR BIOLOGY, a research core providing transgenic and gene knockout facilities. Specific interests include gastrointestinal hormones, receptors, transporters, intestinal development and differentiation and consultation to investigators wishing to characterize membrane proteins; 3) FLUORESCENT PROBE, a research core providing instrumentation and consultation for investigators wishing to use imaging techniques to study intracellular transport and signal transduction in hepatocytes and other epithelial cells; and 4) ADMINISTRATION CORE has established a close working relationship with GRASP Center Investigators, allowing it to successfully fulfill its role as the focal point of Center organizational activities. It identifies, acquires and disseminates information regarding new funding sources, it provides word processing services and generates Lotus budget templates to GRASP investigators for papers and grant applications related to the Center, and also assists investigators in retrieving information from the Sponsored Program Information Network (SPIN), an automated dated base which identifies both private and public funding sources. Interactions within and among Cores has been extensive by shared scientific interests and equipment, the proximity of our laboratories to one another, and the Administrative Core. Through the awarding of Pilot Feasibility grants the center has encouraged a large number of investigators to direct their research to digestive diseases, and this has expanded Core utilization. Additional interactions have occurred through the Center's Program Enrichment activities which include the sponsorship of visiting scientists, lectures and conferences. Basic science research done by GRASP investigators has not only advanced understanding of physiologic mechanisms of the intestine and liver, but has direct relevance to digestive diseases and other public health issues. We support programs in clinical and basic projects in AIDS and HIV pathogenesis, gastrointestinal hormones and their receptors, developmental biology of entero-endocrine and gut epithelial cells, liver cell transport system, cystic fibrosis, and cell biology and molecular mechanisms of infections caused by bacteria and parasites.